Systematic transethnic profiling of anticytokine and anti-leukocyte trafficking for the detection of drug-specific response signatures in the treatment of inflammatory bowel disease.

炎症性肠病（IBD）是一种常见的慢性免疫介导性屏障疾病。目前使用抗细胞因子抗体（TNF-a, IL-23/IL-12）的治疗干预反映了破坏炎症免疫病理特异性途径的意图。因此，个体对生物治疗的反应可以在系统生物学方法中被利用，该方法采用靶向作用机制（MOA）来破译不同疾病实体背景下治疗反应的分子特征，以描述疾病和药物反应的共同和独特转录特征。使用翻译方法（包括来自外周血单核细胞和粘膜活检的DNA全外环测序和RNA全转录组测序，识别药物给药前和给药后指定时间点肠道微生物群的药物特异性改变）来研究治疗干扰细胞因子信号和白细胞运输期间的临床和分子表型。我们的目标是追踪药物和治疗特异性反应的共同和独特特征。通过比较德国和中国人群的反应特征，我们旨在破译影响患病器官中个体药物反应的遗传和环境因素。

Inflammatory bowel disease (IBD) is a common, chronic, immune-mediated barrier disease. Current therapeutic interventions with anti-cytokine antibodies (TNF-a, IL-23/IL-12) reflect the intent to disrupt specific pathways of inflammatory immunopathology. Individual responses to biological treatment can thereby be exploited in a systems biology approach that employs a targeted mechanism of action (MOA) to decipher molecular signatures of therapeutic responses in the context of a distinct disease entity to describe common and unique transcriptional signatures of disease and drug-response. Using a translational approach (including whole exorne sequencing of DNA and whole transcriptome sequencing of RNA from peripheral blood mononuclear cells and mucosal biopsies, identifying drugspecific alterations of the gut microbiota before and at indicated time-points after drug administration) to investigateclinical and molecular phenotypes during therapeutic interference with cytokine signaling and leukocyte trafficking, we aim to trace common and unique signatures of drug- and therapy-specific responses. By comparing response signatures in a german and chinese population we aim to decipher genetic and environmental factors that influence individual drug- response in a diseased organ.